Effects of Priming with D-Glucose on Insulin Secretion from Rat Pancreatic Islets: Increased Responsiveness to Other Secretagogues*

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Abstract
Short term exposure to a high concentration of glucose enhances the insulin response to a second stimulation with the sugar. This priming effect of glucose has been further investigated by comparing the insulin-releasing effects of various secretagogues in the perfused rat pancreas before and after previous exposure to 27.7 mM glucose. Priming markedly increased the insulin release to agents whether metabolizable (leucine) or nonmetabolizable (tolbutamide, Ba++, 3-isobutyl-lmethylxanthine, and alloxan). The priming effect was seen both in cases where secretagogues were administered in the complete absence of metabolic substrate and when tested in the simultaneous presence of a low nonstimulatory glucose concentration (3.9 mM). The insulinotropic effects of tolbutamide were examined at concentrations of 50, 200, and 400 μg/ml of the drug, with and without priming. In the absence of priming, 200 and 400 μg/ml were maximally effective. Previous exposure to 27.7 mM glucose enhanced the secretory responses to all concentrations of sulfonylurea several-fold. Priming thus amplified the maximal secretory capacity of tolbutamide. In isolated islets, prelabeled with [3H]adenine, Ba++, leucine, and tolbutamide stimulated insulin secretion and elevated [3H]cAMP levels, as measured at the end of 3-min incubations. Priming with glucose increased insulin release 4-fold or more, while [3H]cAMP was significantly enhanced only in response to Ba++. It is concluded that: 1) priming with glucose confers an increased secretory capacity on the B cell by altering some critical component of the secretory process distal to the stage of specific stimulus recognition, 2) once induced by glucose, priming can be expressed independently of the presence of the sugar in the extracellular medium, and 3) enhancement of cAMP is not a sufficient factor in the mediation of priming.